Name: investigating the effects of antipsychotics and schizotypy on the n400 using event-related potentials and semantic categorization
Uploaded: 2014-11-19T15:00:00.000+00:00
Duration: 12 min
Description: Watch this Scientific Journal Video about Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization at JoVE.com

The authors would like to acknowledge the Brain and Behavior Research Foundation for their generous support.

This protocol follows the guidelines set forth by the Douglas Institute Research and Ethics Board.
1. Patient Preparation
<ol>
	<li>When the participant arrives, explain the experiment and obtain a signature on an informed consent form that has received ethics approval from the institutions&#8217; Institutional Review Board.</li>
	<li>Make a mark using the red pencil at the bridge of the nose (nasion), in between the eyebrows. Using a tape measure, measure from the nasion to the lower base of the skull, the inion. Discern this location by sliding a hand up the neck until a bump on the back of the participant&#8217;s head is felt.</li>
	<li>Take 1/10th of the measurement between the nasion and the inion and make a mark up near the hairline from the nasion, taking care to ensure that these measurements are in line with the nose.</li>
	<li>Wrap the Head Measuring Tape (4 Color ribbon) around the head at the level of the mark made in Step 1.3. Determine cap size based on where the non-colored end of the ribbon meets the colored end: use a blue cap if it crosses in the blue region, use a blue-red cap if it crosses between the blue and red regions, etc.</li>
</ol>
2. Electrode Placement
<ol>
	<li>Place the cap onto the participant&#8217;s head. Line up the two electrodes at the front of the cap with the eyes. Insert the disposable sponge disks on the frontal electrodes (FP1 and FP2), to keep the electro-gel from spreading.</li>
	<li>Hold the two frontal electrodes against the mark near the hairline and pull the cap over the head. Ensure that the cap fits snugly on the participants head.</li>
	<li>Place the ear electrodes onto the participant&#8217;s earlobes as reference electrodes. Clean the earlobes with alcohol. Using a cotton tip applicator, spread EEG abrasive skin prepping gel onto the earlobes to facilitate conductivity.</li>
	<li>Take a syringe and fill it with electrolyte gel. Then, squeeze the gel onto the ear electrode. Carefully place the gel-filled ear electrode onto the participant&#8217;s earlobes.</li>
	<li>Attach the wires from the cap and the ear electrodes to the EEG amplifier. Set the gain of the amplifier to 20,000. Attach the harness to the cap with the cap straps, making sure that it is snugly keeping the cap in place.</li>
	<li>Start applying electrolyte gel to the ground electrode, which is found in the middle anterior of the cap. Electrolyte gel increases the electrical connectivity between the scalp and the electrode.</li>
	<li>Use the syringe to squeeze electrolyte gel into the electrode. Start by inserting the syringe into the electrode and rock it back and forth until it is in contact with the scalp. Then, simultaneously squeeze the syringe and pull up, creating a vertical column of gel.</li>
	<li>Repeat Step 2.7 for all of the electrodes.</li>
	<li>Abrade the scalp underneath the electrodes with a blunt needle. Do this while observing the computer monitor, which should display a schematic of the electrodes. Aim to scratch the scalp until the corresponding electrode on the screen turns black in color. It is recommended to start with the ear electrodes, and then move on to the ground electrodes.</li>
</ol>
3. Electroencephalography EEG Experiment
<ol>
	<li>Read the instructions for the experiment to the subject. Open the EEG acquisition software on the computer.</li>
	<li>Observe the resting activity of the electrodes. Troubleshoot for &#8220;bad&#8221; electrodes, such as flat line signals, or excessively active signals. If there are any, repeat Steps 2.7 and 2.9 to minimize impedance. 
	strong&#62;NOTE: The impedance, which is measured using a 30 Hz current, should be kept below 5 k&#8486;.</li>
	<li>Begin recording once the electrode signals look good and there are no flat line signals or excessively active signals. Look for any myograms or eye movement, and ensure that the participant refrains from blinking and tensing their jaw and forehead muscles, as these will produce excessive noise in the data. At rest, there may be beta and alpha rhythms present.</li>
	<li>Start the experiment on the second computer. The timing of the experimental design is important. Observe carefully to ensure that the experiment software, such as E-Prime, sends &#8220;markers&#8221; to indicate stimulus onset. This is crucial as stimulus onset is often used as a reference point for an event in ERP paradigms.</li>
	<li>Once the experiment is complete, ensure that the data has been saved- this process will differ depending on the software used. Carefully remove the cap, and assist the participant with hair washing and drying.</li>
	<li>Detach the cap and ear electrodes from the amplifier, remove the disposable sponge disks, and clean the cap and ear electrodes under running water using a stick or the end of a cotton swab. Use a mild soap or shampoo, as well as a toothbrush, to gently clear the gel from the electrodes. Rinse thoroughly. Allow the equipment to air dry.</li>
</ol>
4. Data Processing
<ol>
	<li>To obtain ERP components from the EEG, determine which epoch will be studied. For example, to compute the N400 amplitude, use the mean voltages in the 300-500 msec time-window for calculation.</li>
	<li>Before averaging the EEG epochs, reject trials with excessive eye movements or amplifier saturations. Depending on the experiment paradigm, it may be relevant to reject trials that correspond to incorrect responses.</li>
	<li>After averaging, filter the ERPs and plot the data (see Animated Figure 1 for specific instructions on data processing using Matlab, EEGLab, and ERPLab).</li>
</ol>

<ol>
	<li>Debruille, J. B., Rodier, M., Prevost, M., Lionnet, C., Molavi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+a+small+dose+of+olanzapine+on+healthy+subjects+according+to+their+schizotypy:+an+ERP+study+using+a+semantic+categorization+and+an+oddball+task.">Effects of a small dose of olanzapine on healthy subjects according to their schizotypy: an ERP study using a semantic categorization and an oddball task.</a> Europeam Neuropsychopharmacology. 23 (5), 339-350 (2013).</li><li>Bressler, S. L., Arbib, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Handbook of Brain Theory and Neural Networks. , 412-415 (2002).</li><li>Peterson, N. N., Schroeder, C. E., Arezzo, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+generators+of+early+cortical+somatosensory+evoked+potentials+in+the+awake+monkey.">Neural generators of early cortical somatosensory evoked potentials in the awake monkey.</a> Electroencephalography and Clinical Neurophysiology. 96 (3), 248-260 (1995).</li><li>Blackwood, D. H., Muir, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+brain+potentials+and+their+application.">Cognitive brain potentials and their application.</a> The British Journal of Psychiatry Supplement. 9, 96-100 (1990).</li><li>Debruille, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+N400+potential+could+index+a+semantic+inhibition.">The N400 potential could index a semantic inhibition.</a> Brain Research Reviews. 56 (2), 472-477 (2007).</li><li>Kutas, M., Hillyard, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A.Event-Related+Brain+Potentials+(ERPs)+Elicited+by+Novel+Stimuli+during+Sentence+Processing.">A.Event-Related Brain Potentials (ERPs) Elicited by Novel Stimuli during Sentence Processing.</a> Annals of the New York Academy of Sciences. 425 (1), 236-241 (1984).</li><li>Holcomb, P. J., Kounios, J., Anderson, J. E., West, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-coding,+context-availability,+and+concreteness+effects+in+sentence+comprehension:+an+electrophysiological+investigation.">Dual-coding, context-availability, and concreteness effects in sentence comprehension: an electrophysiological investigation.</a> Journal of Experimental Psychology: Learning, Memory, and Cognition. 25, 721-742 (1999).</li><li>Renoult, L., Brodeur, M. B., Debruille, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Semantic+processing+of+highly+repeated+concepts+presented+in+single-word+trials:+electrophysiological+and+behavioral+correlates.">Semantic processing of highly repeated concepts presented in single-word trials: electrophysiological and behavioral correlates.</a> Biological Psychology. 84, 206-220 (2010).</li><li>Prevost, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Schizotypal+traits+and+N400+in+healthy+subjects.">Schizotypal traits and N400 in healthy subjects.</a> Psychophysiology. 47, 1047-1056 (2010).</li><li>Sur, S., Sinha, V. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Event-related+potential:+An+overview.">Event-related potential: An overview.</a> Industrial Psychiatry Journal. 18 (1), 70-73 (2009).</li><li>Condray, R., Siegle, G. J., Cohen, J. D., van Kammen, D. P., Steinhauer, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+activation+of+the+semantic+network+in+schizophrenia:+evidence+from+event-related+brain+potentials.">Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials.</a> Biological Psychiatry. 54, 1134-1148 (2003).</li><li>Condray, R., Steinhauer, S. R., Cohen, J. D., van Kammen, D. P., Kasparek, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+language+processing+in+schizophrenia:+effects+of+context+and+haloperidol+on+the+event-related+potential.">Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential.</a> Biological Psychiatry. 45, 1336-1355 (1999).</li><li>Light, G. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electroencephalography+(EEG)+and+event-related+potentials+(ERPs)+with+human+participants.">Electroencephalography (EEG) and event-related potentials (ERPs) with human participants.</a> Current Protocols in Neuroscience. , 21-24 (2010).</li><li>Luck, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> An Introduction to the Event-Related Potential Technique. , (2005).</li><li>Luck, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> An Introduction to the Event-Related Potential Technique. , (2005).</li></ol>

The authors have nothing to disclose.

In our investigation of the effects of antipsychotic medication on the N400, we found that in the placebo condition, anterior N400s were larger in individuals with high schizotypy than in the subjects with low schizotypy. In the medication condition however, fronto-central N400s were smaller, but only in the individuals with high schizotypy. Thus, the medication was seen to decrease these large fronto-central N400s in high schizotypal individuals, which confirms previous research illustrating smaller anterior N400s in schizophrenic patients treated with antipsychotic medication, relative to patients receiving a placebo11,12. In individuals with low schizotypy, there was no effect of medication. These findings were obtained with the proper implementation of the protocol, and speak to the importance of collecting clear and precise data.
To ensure accurate and valid results, there are a few critical points to keep in mind. To get a good signal, it is crucial that the cap is snugly fit and placed so that the sagittal electrodes are exactly in the middle and that impedance is adjusted. A cap that is too large can reduce the recording quality, as it will be much harder to reduce impedances13. It is also important that the participants understand that they must avoid excessive movement, blinking, or flexing their face and jaw muscles, as these actions will introduce changes in the EEG traces and potentially make data interpretation very difficult14. After the experiment, the equipment must be properly cleaned to ensure that the electrodes are not blocked with gel residue, which could affect future signal collection.

If there are problems in the signal, such as noise or flat lines, check to make sure that both the ground and reference electrodes are properly connected. Reducing the impedance of these electrodes can reduce noise, so if there are problems in the connectivity, reapply the gel and re-scratch the scalp underneath the electrodes. If there are myograms, allow the subject to relax before proceeding. In designing the experiment, it is relevant for ERP recording that the experimental design accounts for timing aspects, such as the duration of stimulus presentation and brief time periods that allow the participant to blink.

Before beginning an EEG experiment, it is important to understand the associated limitations. The relatively poor spatial resolution may be something to consider, as well as the difficulty of using EEG to elucidate subcortical activity. The noise introduced by blinks and muscle activity is also disadvantageous, and the neural signals obtained are smudged as they pass through the cerebrospinal fluid, meninges, and skull. These limitations may be addressed with alternative neuroimaging methods independently&#8211; such as fMRI, NIRS &#8211; or by combining EEG with these alternate approaches. However, as previously mentioned, these approaches also carry their own limitations. The requisite contrast conditions and the lack of baseline and polarity in fMRI are notable examples. With respect to alternative brain imaging techniques, ERP recording has many advantages- most particularly its remarkable temporal resolution, which is at the level of milliseconds. It is also non-invasive and minimally uncomfortable for the participant, and is not associated with any significant risks or dangers. ERP recording is economically sound, especially when compared to other neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) 15. It offers a look into the neural events that occur in cognitive, sensory, and motor processes, and in the future, could be applied to explore preconscious processes.

While neuroimaging advances have undeniably augmented our understanding of the functions of the brain, these advances have a largely static emphasis on elucidating the structures of the brain. This subsequently leaves the dynamic temporal features of brain networks relatively shrouded in obscurity, as neuroimaging methods that do address these temporal aspects, such as fMRI and near-infrared spectroscopy (NIRS), produce temporal resolutions that are inadequate compared to that of EEG. It is thus pertinent to better understand and employ the use of ERP recording, which is able to produce vast amounts of meaningful information that otherwise would be unknown. ERP recording is a non-invasive analytical tool that allows cognitive neuroscientists to track the rapid temporal modulations of neural activity that are elicited by cognitive, sensory, and motor processes. It involves placing electrodes on the scalp to capture the electrical postsynaptic responses of large neuronal populations2 to specific events or stimuli. ERPs are electroencephalographic changes that are time-locked to sensory, motor, or cognitive events, and are believed to represent the summation of postsynaptic potentials produced during information processing3. These ERP waveforms are characterized by their latency, amplitude, polarity, and scalp distribution, providing a rich array of neurological data that may stimulate further insight into the neural connections that contribute to cognition.

The goal of ERP recording and electroencephalography (EEG) is to obtain information about the foundational neural processes involved in higher-order, complex cognitive operations4. ERPs are defined by their negative or positive fluctuation, as well as their location on the scalp and the time in which they appear after the onset of the stimulus. Various ERPs have been associated with different aspects of cognitive processing. For example, we have been looking at the N400 event-related brain potential5, a negative waveform that is elicited 400 ms after the onset of meaningful stimuli such as words6, and whose distribution on the scalp is known to depend on the semantic category of these stimuli. The N400 is an index of semantic activations, and studies have shown that it has a larger amplitude for words which activate more representations, such as concrete words (e.g., banana) that activate both visual and verbal representations, than for abstract words (e.g., idea), which activate only verbal representations7,8. Research also supports the idea that even mild symptoms of schizophrenia, as measured by schizotypy scales, are associated with abnormally excessive semantic activation of the N4009. As such, we are exploring whether antipsychotic medication, which decreases schizophrenic symptom presentation, normalizes abnormal semantic activations of the N400 in healthy individuals with high levels of schizotypy. Here, the use of ERPs in a semantic categorization paradigm is advantageous for studying the effects of antipsychotics on the N400.

As ERP recording is a non-invasive and relatively economical method to assess neural functioning, it can be applied in a wide range of domains, as evidenced by the substantial number of ERP studies in cognitive neuroscience, neurology, neuropsychology, psycholinguistics, and cognitive psychology. Its versatility enables investigators to ask pertinent research questions about the relative timing of neural events in a large variety of domains, including language, cognition, and the study of various psychiatric disorders10 such as schizophrenia, bipolar affective disorder, depression, and alcohol dependence disorder, and it offers substantial advantages over alternative methods of neuroimaging, such as functional magnetic resonance imaging (fMRI). Some of these include its excellent temporal resolution, which elucidates brain activity down to the millisecond. ERP recording also directly indexes excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) through which many brain computations are performed, something that fMRI does not do. Another advantage of ERP recording is that it offers the possibility of distinguishing inhibitory activity (neuronal hyperpolarizations) from excitatory activity (neuronal depolarization), whereas in fMRI, greater signals are not clearly differentiated between these two. Further, the ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. ERP recordings&#8217; utility, relative cost-effectiveness and associated advantages offer strong rationale for the use of ERPs in cognitive neuroscience as a way to track rapid temporal changes in neural activity. Followed is a step-by-step guide to the basics of running an EEG experiment and recording event-related potentials.

<table><tbody><tr><td>EEG acquisition software (Scan 4.5)</td><td>Neuroscan</td><td>http://www.neuroscan.com/scan.cfm</td><td></td></tr><tr><td>Digital EEG Amplifier (NuAmp)</td><td>Neuro Scan Labs</td><td>&lt;a href=&quot;http://www.neuroscan.com/documents/AF573-01%20CURRY%20NuAmpsExpressPRESSD4.pdf&quot;&gt;http://www.neuroscan.com/documents/AF573-01%20CURRY%20NuAmpsExpressPRESSD4.pdf&lt;/a&gt;</td><td></td></tr><tr><td>2 computers</td><td></td><td></td><td></td></tr><tr><td>Matlab</td><td>The MathWorks, Inc</td><td>&lt;a href=&quot;http://www.mathworks.com/products/matlab/&quot;&gt;http://www.mathworks.com/products/matlab/&lt;/a&gt;</td><td></td></tr><tr><td>EEGLab Matlab toolbox</td><td></td><td>http://sccn.ucsd.edu/eeglab/</td><td></td></tr><tr><td>ERPLAB Toolbox</td><td></td><td>&lt;a href=&quot;http://erpinfo.org/erplab&quot;&gt;http://erpinfo.org/erplab&lt;/a&gt;</td><td></td></tr><tr><td>Stimulus generation software</td><td>E-Prime</td><td></td><td></td></tr><tr><td>ECI Electrode cap</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/caps/</td><td></td></tr><tr><td>Special Head Measuring Tape (4 Colour ribbon)</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>Disposable Sponge Disks</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>EEG Abrasive Skin Prepping Gel (Nuprep)</td><td>Weaver and Company</td><td>http://www.weaverandcompany.com/nuprep.html</td><td></td></tr><tr><td>Body harness</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>Cap straps</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>Electro-gel</td><td>Electro-cap International, Inc</td><td></td><td></td></tr><tr><td>Blunt needle (BD Vacutainer PrecisionGlide Multiple Sample Needle)</td><td>Becton, Dickinson and Company</td><td>367211; see http://www.bd.com/resource.aspx?IDX=7559</td><td></td></tr><tr><td>Syringe</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>2 Ear Electrodes</td><td>Electro-cap International, Inc</td><td>http://www.electro-cap.com/index.cfm/supplies/</td><td></td></tr><tr><td>Alcohol wipes</td><td></td><td></td><td></td></tr><tr><td>Red pencil</td><td></td><td></td><td></td></tr><tr><td>Cotton swabs</td><td></td><td></td><td></td></tr><tr><td>Facilities and supplies for participants to wash their hair after the experiment- sink, shampoo, comb, towels, hair dryer</td><td></td><td></td><td></td></tr></tbody></table>

investigating the effects of antipsychotics and schizotypy on the n400 using event-related potentials and semantic categorization

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in part because of its excellent spatial resolution, which allows researchers to identify brain areas associated with specific cognitive processes. However, in the quest to localize brain functions, it is relevant to note that many cognitive, sensory, and motor processes have temporal distinctions that are imperative to capture, an aspect that is left unfulfilled by fMRI&#8217;s suboptimal temporal resolution. To better understand cognitive processes, it is thus advantageous to utilize event-related potential (ERP) recording as a method of gathering information about the brain. Some of its advantages include its fantastic temporal resolution, which gives researchers the ability to follow the activity of the brain down to the millisecond. It also directly indexes both excitatory and inhibitory post-synaptic potentials by which most brain computations are performed. This sits in contrast to fMRI, which captures an index of metabolic activity. Further, the non-invasive ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. While it is limited by its poor spatial and subcortical activity resolution, ERP recordings&#8217; utility, relative cost-effectiveness, and associated advantages offer strong rationale for its use in cognitive neuroscience to track rapid temporal changes in neural activity. In an effort to foster increase in its use as a research imaging method, and to ensure proper and accurate data collection, the present article will outline &#8211; in the framework of a paradigm using semantic categorization to examine the effects of antipsychotics and schizotypy on the N400 &#8211; the procedure and key aspects associated with ERP data acquisition.

Five figures have been included to aid researchers in obtaining optimal ERP recording. Figure 1 depicts ERP waveforms obtained following successful completion of this protocol; it constitutes a &#8220;good&#8221; result due to its accurate recording. Figure 2 on the other hand, illustrates ERP waveforms that would characterize a poor execution of the protocol, resulting in &#8220;bad&#8221; results, which are most notably identified in excessively noisy signals. Figure 3 shows the common problems that may arise in ERP recording that can impede proper data collection. High activity can be interpreted in the high frequency and large amplitudes in the waves. In contrast, a &#8220;flatline&#8221; indicates a lack of activity or improper connectivity. Figures 4 and 5 show the grand averages for the main results of our investigation into the effects of antipsychotics and schizotypy on the N400, as measured using a semantic categorization paradigm.
<img alt="Figure 1" src="/files/ftp_upload/52082/52082fig1highres.jpg" /> 
Figure 1.&#160;Good Result. This figure depicts the averaged ERP waveforms of one subject over all trials following successful execution of the technique, resulting in no flat lines or excessive noise. Note that the waves will look slightly different depending on the experimental paradigm used- tasks that rely heavily on different processes (cognitive, sensory, and motor) will produce different waveforms depending on the content of the task and the skills required by the task. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/52082/52082fig2highres.jpg" /> 
Figure 2.&#160;Poor Result. This figure depicts the averaged ERP waveforms of one subject over all trials following inadequate execution of the technique. The waveforms shown here are poor due to the noise, as well as the flat line in FP2. Note also the lack of recognizable ERP components in the EEG. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/52082/52082fig3highres.jpg" /> 
Figure 3. Common Problems. This figure depicts the common problems that arise with this technique; namely, eye movement, muscle movement, or saturation. Note that these problems can occur in any of the channels, so be sure to check all of them. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" src="/files/ftp_upload/52082/52082fig4highres.jpg" /> 
Figure 4. Effect of Schizotypy. This figure depicts the grand average ERPs in the placebo condition. Red lines correspond to participants with high scores on the schizotypal personality questionnaire. Black lines correspond to participants with low schizotypy as determined by the questionnaire.
<img alt="Figure 5" src="/files/ftp_upload/52082/52082fig5highres.jpg" /> 
Figure 5. Effects of medication in high schizotypy individuals. This figure depicts the grand average ERPs, where red corresponds to medication (Olanzapine), and black corresponds to placebo. <a href="https://www.jove.com/files/ftp_upload/52082/EEGLab_Tutorial.mp4" target="_blank">Please click here to view a larger version of this figure.</a>
Animated Figure 1. This figure can be used as a guide for processing the data and obtaining ERPs.

Watch this Scientific Journal Video about Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization at JoVE.com

Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization

Using event-related EEG potentials (ERPs), we investigate the effects of antipsychotic medications on abnormal semantic brain activations in healthy individuals with schizotypal traits. We use ERPs to track distinct changes in brain activity, shedding insight into the cognitive processes associated with semantic categorization.

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in ...

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12.8K Views.  McGill University. Using event-related EEG potentials (ERPs), we investigate the effects of antipsychotic medications on abnormal semantic brain activations in healthy individuals with schizotypal traits. We use ERPs to track distinct changes in brain activity, shedding insight into the cognitive processes associated with semantic categorization.

Video: Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization

P50 Sensory Gating in Infants

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating.
Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is &#34;gated&#34;). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits.
Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.

Methods to record auditory P50 sensory gating, a physiological marker of cerebral inhibition which reflects early stages of attention, are described.

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood ...

High Density Event-related Potential  Data Acquisition in Cognitive Neuroscience

Functional magnetic resonance imaging (fMRI) is currently the standard method of evaluating brain function in the field of Cognitive Neuroscience, in part because fMRI data acquisition and analysis techniques are readily available. Because fMRI has excellent spatial resolution but poor temporal resolution, this method can only be used to identify the spatial location of brain activity associated with a given cognitive process (and reveals virtually nothing about the time course of brain activity). By contrast, event-related potential (ERP) recording, a method that is used much less frequently than fMRI, has excellent temporal resolution and thus can track rapid temporal modulations in neural activity. Unfortunately, ERPs are under utilized in Cognitive Neuroscience because data acquisition techniques are not readily available and low density ERP recording has poor spatial resolution. In an effort to foster the increased use of ERPs in Cognitive Neuroscience, the present article details key techniques involved in high density ERP data acquisition. Critically, high density ERPs offer the promise of excellent temporal resolution and good spatial resolution (or excellent spatial resolution if coupled with fMRI), which is necessary to capture the spatial-temporal dynamics of human brain function.

Event-related potential (ERP) recording is under utilized in Cognitive Neuroscience because data acquisition techniques are not readily available and this method often has poor spatial resolution. To foster the increased use of ERPs in Cognitive Neuroscience, the present article details key techniques involved in high density ERP data acquisition.

Functional magnetic resonance imaging (fMRI) is currently the standard method of evaluating brain function in the field of Cognitive Neuroscience, in part ...

Neuroscience

Development of a Virtual Reality Assessment of Everyday Living Skills

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; Treatment studies aimed at cognitive impairment in patients with schizophrenia not only require demonstration of improvements on cognitive tests, but also evidence that any cognitive changes lead to clinically meaningful improvements.&#160; Measures of &#8220;functional capacity&#8221; index the extent to which individuals have the potential to perform skills required for real world functioning. &#160;Current data do not support the recommendation of any single instrument for measurement of functional capacity.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a novel, interactive gaming based measure of functional capacity that uses a realistic simulated environment to recreate routine activities of daily living. Studies are currently underway to evaluate and establish the VRFCAT&#8217;s sensitivity, reliability, validity, and practicality.&#160;This new measure of functional capacity is practical, relevant, easy to use, and has several features that improve validity and sensitivity of measurement of function in clinical trials of patients with CNS disorders.

A challenge for proving treatment efficacy for cognitive impairments in schizophrenia is finding the optimizing measurement of skills related to everyday functioning.&#160; The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is an interactive gaming based computerized measure aimed at skills associated with everyday functioning, including baseline impairments and treatment related changes.

Cognitive impairments affect the majority of patients with schizophrenia and these impairments predict poor long term psychosocial outcomes.&#160; ...

Methods to Explore the Influence of Top-down Visual Processes on Motor Behavior

Kinesthetic awareness is important to successfully navigate the environment. When we interact with our daily surroundings, some aspects of movement are deliberately planned, while others spontaneously occur below conscious awareness. The deliberate component of this dichotomy has been studied extensively in several contexts, while the spontaneous component remains largely under-explored. Moreover, how perceptual processes modulate these movement classes is still unclear. In particular, a currently debated issue is whether the visuomotor system is governed by the spatial percept produced by a visual illusion or whether it is not affected by the illusion and is governed instead by the veridical percept. Bistable percepts such as 3D depth inversion illusions (DIIs) provide an excellent context to study such interactions and balance, particularly when used in combination with reach-to-grasp movements. In this study, a methodology is developed that uses a DII to clarify the role of top-down processes on motor action, particularly exploring how reaches toward a target on a DII are affected in both deliberate and spontaneous movement domains.

It is unclear how top-down signals from the ventral visual stream affect movement. We developed a paradigm to test motor behavior towards a target on a 3D depth inversion illusion. Significant differences are reported in both deliberate, goal-directed movements and automatic actions under illusory and veridical viewing conditions.

Kinesthetic awareness is important to successfully navigate the environment. When we interact with our daily surroundings, some aspects of movement are ...

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.

This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR).&#160;FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with ...

A Semantic Priming Event-related Potential (ERP) Task to Study Lexico-semantic and Visuo-semantic Processing in Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) have characteristic deficits in understanding the meaning of language, or semantic processing. However, some evidence indicates that semantic processing of non-linguistic stimuli is intact, suggesting that semantic deficits may be language-specific. To appropriately characterize semantic processing deficits in individuals with ASD, comparison of within-modality linguistic (e.g., written words) and non-linguistic (e.g., pictures) stimuli is required. This paper describes such a methodology that makes use of a semantic priming paradigm during concurrent recording of electroencephalographic (EEG) data. EEG provides a dynamic measure of brain activity that is well-suited to characterize subtle differences in semantic processing that may not be observable at the behavioral level. The semantic priming paradigm presents a prime picture or word (e.g., dog) followed by a target picture or word that is either related (e.g., cat) or unrelated (e.g., pencil) to the prime. This paradigm can thus be used to evaluate semantic processing across different modalities, and to compare lexico-semantic and visuo-semantic processing abilities in individuals with ASD and how they might differ from TD individuals. The specific steps involved in creating the stimuli, performing the EEG testing, and analyzing the EEG data are discussed. Representative results illustrate how the N400 component of the event-related potential (ERP) is reduced following semantically-related prime-target pairs compared to unrelated pairs. Comparisons of the N400 between conditions, modalities, and groups can provide estimates of the success of semantic processing, and can thereby be used to characterize semantic deficits in individuals with ASD or other clinical populations.

A Semantic Priming Event-related Potential ERP Task to Study Lexico-semantic and Visuo-semantic Processing in Autism Spectrum Disorder

This paper describes a semantic priming ERP task using within-modality pairs of pictures and words to investigate semantic processing in individuals with autism spectrum disorder (ASD).

Individuals with autism spectrum disorder (ASD) have characteristic deficits in understanding the meaning of language, or semantic processing. However, ...

Dissociation of the Confounding Influences of Expectancy and Integrative Difficulty Residing in Anomalous Sentences in Event-related Potential Studies

The confounding factors of unexpectedness and semantic integration difficulty naturally residing in anomalous sentences in language studies make it difficult to determine the underlying processing mechanism of ERP components. Unlike the traditional static approach of manipulating expectancy through corpus frequency or cloze probability, this protocol proposes a dynamic method to enhance participants&#39; expectancy for rarely-met anomalous sentences by multiple repetitions while maintaining their semantic integration difficulties. To address the time cost increase resulting from multiple repetitions, this protocol proposes to repeat only the strictly simplified core structure extracted from the anomalous sentence before presenting the semantically enriched, much more informative complete anomalous sentence containing the anomalous core structure to reinitiate the semantic integration processing. The complete anomalous sentence elicited a P600 effect. It suggests that the participants did not give up processing the anomalous information after repetitions and the same semantic integration difficulty was successfully reinitiated. Importantly, the representative experimental results reveal that the greatly attenuated N400 effect caused by multiple repetitions was not recovered by the follow-up reinitiated semantic integration difficulty. It suggests that the attenuated N400 effect should be mainly attributed to the enhancement of expectancy for anomalous information by multiple repetitions. The experimental results show that this method can effectively enhance participants&#39; expectancy for anomalous sentences while retaining the semantic integration difficulty.

We present a protocol to dissociate the intertwining factors of integrative difficulty and unexpectedness in semantically anomalous sentences by applying multiple repetitions to enhance participant&#39;s expectancy for anomalous sentences. The dissociation helps to investigate the major contributor of elicited event-related potentials (ERP) effects such as N400 in language studies.

The confounding factors of unexpectedness and semantic integration difficulty naturally residing in anomalous sentences in language studies make it ...

Interaction between Phonological and Semantic Processes in Visual Word Recognition using Electrophysiology

Controversies have always existed in research related to reading abilities; on whether printed words are perceived in a feedforward manner based on orthographic information after which, other representations, such as phonology and semantics are activated, or whether these are fully interactive and high-level semantic information affects early processing. An interference paradigm was implemented in the presented protocol of phonological and semantic judgment tasks that utilized the same precede-target pairs to explore the relative order of phonological and semantic activation. The high- and low-frequency target words were preceded with three conditions: semantically related, phonological-related (homophones), or unrelated. The results showed that the induced P200 component of low-frequency word pairs was significantly greater than high-frequency words in both the semantic and phonological tasks. In addition, both the homophones in the semantic task and the semantically related pairs in the phonological task caused reduction in N400 when compared to the the control condition, word frequency-independently. It is worth noting that for the low-frequency pairs in the phonological judgment task, the P200 released by the semantically related word pairs was significantly larger than that in the control condition. Overall, semantic processing in phonological tasks and phonological processing in semantic tasks were found in both high- and low-frequency words, suggesting that the interaction between semantics and phonology may operate in a task-independent manner. However, the specific time this interaction occurred may have been affected by the task and frequency.

We present a protocol to explore the relative activation sequence of phonology and semantics in visual word recognition. The results show that consistent with interactive accounts, semantic and phonological representations may be processed interactively, and higher-level linguistic representations may affect early processing.

Controversies have always existed in research related to reading abilities; on whether printed words are perceived in a feedforward manner based on ...

How to Find Effects of Stimulus Processing on Event Related Brain Potentials of Close Others when Hyperscanning Partners

The partners of each pair must be able to pass the McGill Friendship Questionnaire without communicating. Each partner is then seated in front of a screen in one of two adjacent rooms. These rooms are separated by a glass window through which participants communicate to maintain feelings of togetherness while being fitted with the EEG cap. After checking for adequate EEG signals, the glass is covered by a curtain to prevent visual communication. Then, partners must be silent but are instructed to try to feel in the presence of their partner during the entire experiment. Just before it starts, participants are told that each of them will be presented with one image at a time and that these images will occur at the same time for both of them on their own screen. They are also instructed that, for each trial, the simultaneous images will always be different. However, unbeknownst to them, trials are randomized: only half of them are consistent with this instruction and actually include two different images. These trials form the DSC, that is, the different-stimuli condition. The other half of the trials are inconsistent with the instruction. They include two identical images and form the ISC (identical-stimuli condition). After the experiment, participants are sorted into two groups: those who reported that they felt in the presence of their partner during the majority of the trials and those who reported they did not. The impact of the stimulus processing of the partner is found by subtracting the mean voltages of the ERPs of the ISC (inconsistent with the instructions) from the ERPs of the DSC (consistent with the instructions) in at least two time windows (TWs): firstly, in the 75 to 150 ms TW, where the absolute values of these subtractions are greater, especially at right frontal sites, in those who felt in the presence of their partner than in those who did not; secondly, in the LPP time window (i.e., from 650 to 950 ms post onset), where ERPs are significantly less positive in the DSC than in the ISC in those in whom the raw results of the early (75-150ms) subtractions are negative.

This protocol describes key steps involved in assessing the sensitivity of the brain of one person to the stimulus processing of a close other by selecting pairs of partners, recording their electroencephalogram (EEG) simultaneously and computing their event-related brain potentials (ERPs).

The partners of each pair must be able to pass the McGill Friendship Questionnaire without communicating. Each partner is then seated in front of a screen ...

Detecting Pre-Stimulus Source-Level Effects on Object Perception with Magnetoencephalography

Pre-stimulus oscillatory brain activity influences upcoming perception. The characteristics of this pre-stimulus activity can predict whether a near-threshold stimulus will be perceived or not perceived, but can they also predict which one of two competing stimuli with different perceptual contents is perceived? Ambiguous visual stimuli, which can be seen in one of two possible ways at a time, are ideally suited to investigate this question. Magnetoencephalography (MEG) is a neurophysiological measurement technique that records magnetic signals emitted as a result of brain activity. The millisecond temporal resolution of MEG allows for a characterization of oscillatory brain states from as little as 1 second of recorded data. Presenting an empty screen around 1 second prior to the ambiguous stimulus onset therefore provides a time window in which one can investigate whether pre-stimulus oscillatory activity biases the content of upcoming perception, as indicated by participants&#39;&#160;reports. The spatial resolution of MEG is not excellent, but sufficient to localise sources of brain activity at the centimetre scale. Source reconstruction of MEG activity then allows for testing hypotheses about the oscillatory activity of specific regions of interest, as well as the time- and frequency-resolved connectivity between regions of interest. The described protocol enables a better understanding of the influence of spontaneous, ongoing brain activity on visual perception.

This article describes how to set up an experiment that allows detecting pre-stimulus source-level influences on object perception using magnetoencephalography (MEG). It covers stimulus material, experimental design, MEG recording, and data analysis.